Polycystic kidney disease (PKD) is characterized by loss of normal epithelial morphology and function in kidney tubules, and resultant cyst formation. Polycystins 1 and 2 are, therefore, among the groups of molecules required to maintain normal epithelial morphology and function. In our laboratory, a major focus has been on how integrins and cadherins, normally thought of as cell-extracellular matrix (ECM) and cell-cell adhesion molecules, respectively, cooperate to maintain normal epithelial morphology. As a component of these studies, we have recently published that alphas betal integrin, apart from its role as a receptor for laminin, a component of the ECM, also functions as part of the adherens junction where it associates with the cadherin:catenin complex, and stimulates cadherin mediated cell-cell adhesion. In this grant we now turn our focus to the role of integrins and cadherins in PKD, and in particular, how polycystins 1 and 2 may function in signal transduction pathways that affect integrin and cadherin function. Understanding the role of integrins and cadherins in PKD may eventually lead to pharmacological interventions that ameliorate cystogenesis. PKD is a cause of a significant portion of chronic renal failure that leads to dialysis and transplantation. This research aimed at understanding how PKD causes kidney damage, will yield information that should lead to treatments that help prevent kidney damage in PKD.